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Actinobacillus pleuropneumoniae (APP) causes porcine pleuropneumonia (PCP), which is clinically characterized by acute hemorrhagic, necrotizing pneumonia, and chronic fibrinous pneumonia. Although many measures have been taken to prevent the disease, prevention and control of the disease are becoming increasingly difficult due to the abundance of APP sera, weak vaccine cross-protection, and increasing antibiotic resistance in APP. Therefore, there is an urgent need to develop novel drugs against APP infection to prevent the spread of APP. Naringin (NAR) has been reported to have an excellent therapeutic effect on pulmonary diseases, but its therapeutic effect on lung injury caused by APP is not apparent. Our research has shown that NAR was able to alleviate APP-induced weight loss and quantity of food taken and reduce the number of WBCs and NEs in peripheral blood in mice; pathological tissue sections showed that NAR was able to prevent and control APP-induced pathological lung injury effectively; based on the establishment of an in vivo/in vitro model of APP inflammation, it was found that NAR was able to play an anti-inflammatory role through inhibiting the MAPK/NF-κB signaling pathway and exerting anti-inflammatory effects; additionally, NAR activating the Nrf2 signalling pathway, increasing the secretion of antioxidant enzymes Nqo1, CAT, and SOD1, inhibiting the secretion of oxidative damage factors NOS2 and COX2, and enhancing the antioxidant stress ability, thus playing an antioxidant role. In summary, NAR can relieve severe lung injury caused by APP by reducing excessive inflammatory response and improving antioxidant capacity.
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Infecções por Actinobacillus , Actinobacillus pleuropneumoniae , Lesão Pulmonar Aguda , Flavanonas , Proteína 1 Associada a ECH Semelhante a Kelch , Fator 2 Relacionado a NF-E2 , NF-kappa B , Animais , Camundongos , Infecções por Actinobacillus/veterinária , Infecções por Actinobacillus/tratamento farmacológico , Actinobacillus pleuropneumoniae/efeitos dos fármacos , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/prevenção & controle , Flavanonas/uso terapêutico , Flavanonas/farmacologia , Heme Oxigenase-1 , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Proteínas de Membrana , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
Based on mass spectrometry(MS)-guided separation strategy, compound 1 was obtained from the roots of Rhus chinensis. By comprehensive analysis of high resolution-electrospray ionization-mass spectrometry(HR-ESI-MS), nuclear magnetic resonance(NMR) data, and quantum chemical calculation of NMR(qcc-NMR) parameters, compound 1 was elucidated as rhuslactone, a 17-epi-dammarane triterpenoid with a rare 17α-side chain. An HPLC-ELSD method for its quantification in R. chinensis was established and adopted for the quantification of rhuslactone in different batches of R. chinensis. Rhuslactone displayed a good linear relationship within the range of 0.021 3-1.07 µmol·mL~(-1 )(r=0.997 6), and the average recovery was 99.34% [relative standard deviation(RSD) 2.9%). Moreover, the results of the evaluation test of the preventive effects of rhusalctone on coronary heart disease(CHD) and thrombosis showed that rhuslactone(0.11 nmol·mL~(-1)) significantly alleviated heart enlargement and venous congestion and increased cardiac output(CO), blood flow velocity(BFV), and heart rate, thereby reducing thrombus formation in zebrafish with CHD. The effects of rhuslactone on CO and BFV were superior to that of digoxin(1.02 nmol·mL~(-1)), and its effect on improving heart rate was comparable to that of digoxin. This study provides experimental references for the isolation, identification, quality control, and application of rhuslactone from R. chinensis against CHD. It is worth mentioning that this study has discussed some omissions in the determination of the stereochemistry of C-17 in dammarane triterpenoids in the present coursebook Chemistry of Chinese Medicine and some research papers, that is, the compound may be 17-epi-dammarane triterpenoid. This paper has also proposed steps for the establishment of C-17 stereochemistry.
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Doença das Coronárias , Rhus , Trombose , Triterpenos , Animais , Peixe-Zebra , Rhus/química , Triterpenos/análise , DamaranosRESUMO
BACKGROUND: Tuberculosis infection is a major complication of silicosis, but there is no study on whether silicosis can affect the sensitivity of QuantiFERON-TB Gold In-Tube (QFT-GIT) assays. This study will analyze the relationship between silicosis and QFT-GIT, determine the main factor of the QFT-GIT sensitivity decrease in silicosis and explore the methods to increase the sensitivity. METHODS: Silicosis patients with positive tubercle bacillus cultures were collected. The QFT-GIT, flow cytometry and blocking antibodies were used. RESULTS: The sensitivity of QFT-GIT in silicosis patients (58.46%) was significantly decreased and the expression of PD-1 on T cells and CD56+NK cells in pulmonary tuberculosis combined with silicosis were higher than normal tuberculosis patients and silicosis only patients. Further analysis found that the ratio of PD-1+CD4+T and IFN-γwere negatively correlated and blockaded the PD-1 pathway with antibodies can restore the sensitivity of QFT-GIT in silicosis. CONCLUSIONS: This is the first study to analyze the relationship between immune exhaustion and QFT-GIT in silicosis and found that the sensitivity of QFT-GIT was decreased by the expression of PD-1 on lymphocytes. Antibody blocking experiments increased the expression of IFN-γ and provided a new method to improve the sensitivity of QFT in silicosis. The study also found that silicosis can increase PD-1 expression. As PD-1 functions in infectious diseases, it will promote immune exhaustion in silicosis and lead to tuberculosis from latent to active infection. The study provided theoretical evidence for the diagnosis and immunotherapy of silicosis complications, and it has great value in clinical diagnostics and treatment.
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Tuberculose Latente , Silicose , Tuberculose , Humanos , Receptor de Morte Celular Programada 1 , Tuberculose Latente/diagnóstico , Silicose/diagnóstico , Silicose/complicações , Anticorpos Bloqueadores , Linfócitos , Teste Tuberculínico/métodosRESUMO
BACKGROUND: Regulatory T cells (Treg cells) in the peripheral blood of patients with pulmonary tuberculosis (PTB) may be closely related to the progression of PTB. In this study, the distribution characteristics and clinical importance of CD8+CD28- Treg cells in patients with tuberculosis were systematically analyzed, and the role and importance of CD8+CD28- Treg cells in influencing the immune response and progression of tuberculosis were discussed, which will provide immunological indices and reference values for the clinical diagnosis of tuberculosis. METHODS: Flow cytometry, sputum smears and computed tomography imaging were used to analyze the distribution characteristics of CD8+CD28- Treg cells in the peripheral blood of patients with PTB and the correlation between CD8+CD28-Treg cells and clinical and immune indices. RESULTS: The percentages of CD4+CD25high and CD8+CD28- Treg cells in the peripheral blood of patients with PTB were significantly higher than those in the healthy control (HC) group. Further analysis showed that the percentage of CD4+CD25highTreg cells in the Stage II group was significantly higher than that in the HC group. The percentages of CD4+CD25high and CD8+CD28- Treg cells increased significantly in patients in the Stage II group. The proportion of CD8+CD28- Treg cells was directly proportional to the degree of positivity in sputum smears, while CD4+CD25highTreg cells did not exhibit this trend. The correlations between the percentage of CD4+CD25high and CD8+CD28- Treg cells and the percentage of lymphocyte subsets were examined. The percentage of CD8+CD28- Treg cells was negatively correlated with the percentage of CD4+T cells and positively correlated with the CD8+T cell percentage in the HC and PTB groups. The percentage of CD4 + CD25highTreg cells was positively correlated with the percentage of CD4+T cells only in the PTB group. CONCLUSIONS: This study was the first to show that the proportion of CD8+CD28- Treg cells in the peripheral blood of patients with PTB was significantly increased, and the increase in CD8+CD28- Treg cells was related to the progression of PTB, which may affect the proportion of immune cell subsets by inhibiting the immune response, resulting in the progression of PTB.
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Tuberculose Pulmonar , Tuberculose , Antígenos CD28/análise , Linfócitos T CD8-Positivos , Humanos , Linfócitos T ReguladoresRESUMO
OBJECTIVE: To investigate the pathological features and significance of myocardial contraction band necrosis in sudden cardiac death. METHODS: Using HE and PTAH staining, the distribution sites and pathological features of myocardial contraction band necrosis were observed. The data were analyzed according to the extent of necrosis. RESULTS: The locations, pathological features and the extent of necrosis were similar in different sudden death cases. The locations were related with sites of myocardial damage. The papillary muscles of left ventricular were most occurred, followed by the anterior wall of left ventricular. In the sudden death cases caused by stress cardiomyopathy, the extent of myocardial contraction band necrosis was lighter than the others. Most cases were predominantly level 1, the others were level 2. CONCLUSION: Used as the diagnosis basis of acute myocardial ischemia, the myocardial contraction band necrosis has important significance to determination of death.
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Morte Súbita Cardíaca/patologia , Morte Súbita/etiologia , Cardiopatias/mortalidade , Contração Miocárdica/fisiologia , Miocárdio/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença das Coronárias/complicações , Feminino , Cardiopatias/classificação , Cardiopatias/diagnóstico , Cardiopatias/patologia , Humanos , Masculino , Pessoa de Meia-Idade , NecroseRESUMO
Individual stature estimation is one of the most important contents of forensic anthropology. Currently, it has been used that the regression equations established by the data collected by direct measurement or radiological techniques in a certain group of limbs, irregular bones, and anatomic landmarks. Due to the impact of population mobility, human physical improvement, racial and geographic differences, estimation of individual stature should be a regular study. This paper reviews the different methods of stature estimation, briefly describes the advantages and disadvantages of each method, and prospects a new research direction.
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Estatura , Osso e Ossos/anatomia & histologia , Medicina Legal/métodos , Extremidades , Feminino , Antropologia Forense , Humanos , Masculino , Análise de Regressão , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Epithelioid trophoblastic tumor (ETT) is an extremely rare malignant gestational trophoblastic neoplasm commonly presenting with abnormal vaginal bleeding, abdominal pain, and increased human chorionic gonadotropin (hCG). This study reported a case of uterine ETT with the main manifestation being increased hCG. CASE SUMMARY: A 39-year-old female was referred to the Ningbo Maternal and Child Hospital of China in December 2022, complaining of increased hCG levels for 1 month. Magnetic resonance imaging revealed gestational trophoblastic tumor, and hysteroscopic electrotomy and curettage of intrauterine hyperplasia were performed. The patient was diagnosed with uterine ETT through postoperative pathological examination and immunohistochemical results. Total laparoscopic hysterectomy and bilateral salpingectomy were performed, and hCG levels returned to normal. The patient was without recurrence during the postoperative 3-month follow-up. CONCLUSION: This study reported a case of uterine ETT with the main manifestation being increased hCG, highlighting that ETT should be considered in the presence of abnormal hCG. A total laparoscopic hysterectomy is recommended.
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Klebsiella pneumoniae (Kpn) is an important pathogen of hospital-acquired pneumonia, which can lead to sepsis and death in severe cases. In this study, we simulated pneumonia induced by Kpn infection in mice to investigate the therapeutic effect of naringin (NAR) on bacterial-induced lung inflammation. Mice infected with Kpn exhibited increases in white blood cells (WBC) and neutrophils in the peripheral blood and pathological severe injury of the lungs. This injury was manifested by increased expression of the inflammatory cytokines interleukin (IL)- 18, IL-1ß, tumor necrosis factor-α (TNF-α) and IL-6, and elevated the expression of NLRP3 protein. NAR treatment could decrease the protein expression of NLRP3, alleviate lung inflammation, and reduce lung injury in mice caused by Kpn. Meanwhile, molecular docking results suggest NAR could bind to NLRP3 and Surface Plasmon Resonance (SPR) analyses also confirm this result. In vitro trials, we found that pretreated with NAR not only inhibited nuclear translocation of nuclear factor (NF)-κB protein P65 but also attenuated the protein interaction of NLRP3, caspase-1 and ASC and inhibited the assembly of NLRP3 inflammasome in mice AMs. Additionally, NAR could reduce intracellular potassium (K+) efflux, inhibiting NLRP3 inflammasome activation. These results indicated that NAR could protect against Kpn-induced pneumonia by inhibiting the overactivation of the NLRP3 inflammasome signaling pathway. The results of this study confirm the efficacy of NAR in treating bacterial pneumonia, refine the mechanism of action of NAR, and provide a theoretical basis for the research and development of NAR as an anti-inflammatory adjuvant.
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Inflamassomos , Pneumonia , Camundongos , Animais , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Klebsiella pneumoniae , Simulação de Acoplamento Molecular , NF-kappa B/metabolismo , Pneumonia/tratamento farmacológicoRESUMO
Diabetic neuropathic pain (DNP), one of the most common complications of diabetes, is characterized by bilateral symmetrical distal limb pain and substantial morbidity. To compare the differences is aimed at serum metabolite levels between 81 DNP and 73 T2DM patients without neuropathy and found that the levels of branched-chain amino acids (BCAA) are significantly lower in DNP patients than in T2DM patients. In high-fat diet/low-dose streptozotocin (HFD/STZ)-induced T2DM and leptin receptor-deficient diabetic (db/db) mouse models, it is verified that BCAA deficiency aggravated, whereas BCAA supplementation alleviated DNP symptoms. Mechanistically, using a combination of RNA sequencing of mouse dorsal root ganglion (DRG) tissues and label-free quantitative proteomic analysis of cultured cells, it is found that BCAA deficiency activated the expression of L-type amino acid transporter 1 (LAT1) through ATF4, which is reversed by BCAA supplementation. Abnormally upregulated LAT1 reduced Kv1.2 localization to the cell membrane, and inhibited Kv1.2 channels, thereby increasing neuronal excitability and causing neuropathy. Furthermore, intraperitoneal injection of the LAT1 inhibitor, BCH, alleviated DNP symptoms in mice, confirming that BCAA-deficiency-induced LAT1 activation contributes to the onset of DNP. These findings provide fresh insights into the metabolic differences between DNP and T2DM, and the development of approaches for the management of DNP.
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Aminoácidos de Cadeia Ramificada , Diabetes Mellitus Experimental , Neuropatias Diabéticas , Canal de Potássio Kv1.2 , Transportador 1 de Aminoácidos Neutros Grandes , Regulação para Cima , Animais , Aminoácidos de Cadeia Ramificada/metabolismo , Camundongos , Humanos , Masculino , Neuropatias Diabéticas/metabolismo , Neuropatias Diabéticas/genética , Transportador 1 de Aminoácidos Neutros Grandes/genética , Transportador 1 de Aminoácidos Neutros Grandes/metabolismo , Canal de Potássio Kv1.2/genética , Canal de Potássio Kv1.2/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/genética , Modelos Animais de Doenças , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/complicações , Neuralgia/metabolismo , Neuralgia/genética , Feminino , Camundongos Endogâmicos C57BL , Pessoa de Meia-IdadeRESUMO
Six new diterpenoids, identified as two abietane derivatives, euphraticanoids J and K (1 and 2), two pimarane derivatives, euphraticanoids L and M (3 and 4), and two 9,10-seco-abietane derivatives, euphraticanoids N and O (5 and 6) were isolated from Populus euphratica resins. Their structures including absolute configurations were characterized using spectroscopic, quantum chemical NMR, and ECD calculation methods. The anti-inflammatory activity of the compounds was tested and the results revealed that compounds 4 and 6 inhibited the production of iNOS and COX-2 in a dose-dependent manner in lipopolysaccharide (LPS)-induced RAW 264.7 cells.
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Diterpenos , Populus , Abietanos/farmacologia , Estrutura Molecular , Diterpenos/farmacologia , Diterpenos/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Resinas VegetaisRESUMO
Background: Myotonic dystrophy type 1 (DM1) is the most common and dominant inherited neuromuscular dystrophy disease in adults, involving multiple organs, including the brain. Although structural measurements showed that DM1 is predominantly associated with white-matter damage, they failed to reveal the dysfunction of the white-matter. Recent studies have demonstrated that the functional activity of white-matter is of great significance and has given us insights into revealing the mechanisms of brain disorders. Materials and methods: Using resting-state fMRI data, we adopted a clustering analysis to identify the white-matter functional networks and calculated functional connectivity between these networks in 16 DM1 patients and 18 healthy controls (HCs). A two-sample t-test was conducted between the two groups. Partial correlation analyzes were performed between the altered white-matter FC and clinical MMSE or HAMD scores. Results: We identified 13 white-matter functional networks by clustering analysis. These white-matter functional networks can be divided into a three-layer network (superficial, middle, and deep) according to their spatial distribution. Compared to HCs, DM1 patients showed increased FC within intra-layer white-matter and inter-layer white-matter networks. For intra-layer networks, the increased FC was mainly located in the inferior longitudinal fasciculus, prefrontal cortex, and corpus callosum networks. For inter-layer networks, the increased FC of DM1 patients is mainly located in the superior corona radiata and deep networks. Conclusion: Results demonstrated the abnormalities of white-matter functional connectivity in DM1 located in both intra-layer and inter-layer white-matter networks and suggested that the pathophysiology mechanism of DM1 may be related to the white-matter functional dysconnectivity. Furthermore, it may facilitate the treatment development of DM1.
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Norepinephrine (NE) neurons in the locus coeruleus (LC) play key roles in modulating sleep and wakefulness. Recent studies have revealed that the paraventricular thalamic nucleus (PVT) is a critical wakefulness-controlling nucleus in mice. However, the effects of NE on PVT neurons remain largely unknown. Here, we investigated the mechanisms of NE modulating wakefulness in the PVT by using viral tracing, behavioral tests, slice electrophysiology, and optogenetics techniques. We found that the PVT-projecting LC neurons had few collateral projections to other brain nuclei. Behavioral tests showed that specific activation of the LC-PVT projections or microinjection of NE into the PVT accelerated emergence from general anesthesia and enhanced locomotion activity. Moreover, brain slice recording results indicated that NE increased the activity of the PVT neurons mainly by increasing the frequency of spontaneous excitatory postsynaptic currents via α1 adrenoceptors. Thus, our results demonstrate that NE modulates wakefulness via α1 adrenoceptors in the PVT.
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This study aimed to examine the association between famine exposure in different stages of life and the risk of overweight/obesity and abdominal obesity in laterlife. A total of 12,458 participants were categorized into non-exposure and four direct exposures, including fetal, childhood, adolescence, and adult exposure. Only risk of being overweight or obesity in adolescence exposure [odds ratio ( OR), 1.45; 95% confidence interval ( CI), 1.08-1.94] was significantly higher than in non-exposure. Childhood ( OR, 1.27; 95% CI, 1.05-1.54) and adolescence ( OR, 1.53; 95% CI, 1.15-2.05) exposures had significantly an increased risk of abdominal obesity compared with non-exposure. Additionally, different famine severity exposures had different influences on the development of overweight/obesity and abdominal obesity. Famine exposure in adolescence, which was a behavior formative period, can increase the risk of overweight/obesity and abdominal obesity in adulthood, specifically in famine severely affect area.
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Fome Epidêmica , Sobrepeso/epidemiologia , Adolescente , Adulto , Fatores Etários , Idoso , Criança , Pré-Escolar , China , Estudos Transversais , Feminino , Feto/fisiopatologia , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Obesidade/etiologia , Obesidade Abdominal/epidemiologia , Obesidade Abdominal/etiologia , Sobrepeso/etiologia , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND: Netrin-1 is an axon guidance protein, which can inhibit inflammatory reaction and stabilize the blood-brain barrier to protect against experimental brain injury. We evaluated the concentration of netrin-1 in acute intracerebral hemorrhage (ICH) patients and explored whether netrin-1 is a potential prognostic biomarker for ICH. METHODS: This study recruited a total of 126 ICH patients and 126 healthy controls. Netrin-1 concentration was determined using a commercially available human enzyme-linked immune sorbent assay kit. National Institutes of Health Stroke Scale (NIHSS) score and hematoma volume were used to assess hemorrhagic severity. An unfavorable outcome was defined as modified Rankin Scale >2 at 90 days. RESULTS: ICH patients showed significantly lower serum netrin-1 concentrations than controls. Serum netrin-1 concentrations were strongly and inversely correlated with serum C-reactive protein concentrations, NIHSS score and hematoma volume. Multivariate analyses revealed that low netrin-1 concentration was associated with 90-day death, unfavorable outcome and overall survival after adjustment for other confounding variables. Under the receiver operating characteristic curve, serum netrin-1 remarkably discriminated patients at risk of 90-day death and unfavorable outcome. CONCLUSIONS: Serum netrin-1 concentrations are decreased in patients with ICH, and the concentrations of netrin-1 were intimately associated with inflammation, hemorrhagic severity and clinical outcome of ICH.
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Hemorragia Cerebral , Hematoma , Hemorragia Cerebral/diagnóstico , Humanos , Netrina-1 , Prognóstico , Curva ROCRESUMO
OBJECTIVE: The present study aimed to investigate the association of red meat usual intake with metabolic syndrome (MetS), and explore the contribution of red meat usual intake to serum ferritin. METHODS: Based on the data from the longitudinal China Health and Nutrition Survey (CHNS), 2,797 healthy adults aged 18-75 years without hypertension, diabetes, and MetS were selected in 2009 as subjects and follow-up studies were carried out till 2015. We used the National Cancer Institute (NCI) method to estimate the usual intake of foods. Multivariable logistic regressions were performed to evaluate the association between red meat usual intake and the risk of MetS. Quantile regression analysis was used to study the relationship between red meat consumption and serum ferritin levels. RESULTS: After adjusting for potential confounders, red meat, and fresh red meat were positively associated with the risk of MetS ( RR = 1.41, 95% CI: 1.05-1.90 and RR = 1.37, 95% CI: 1.02-1.85, respectively). These relationships showed increasing trend ( P < 0.05). The level of serum ferritin increased significantly with the number of MetS components ( P < 0.05). The quantile regression analysis showed that red meat and fresh red meat usual intake had a significant positive association with serum ferritin levels across the entire conditional serum ferritin distribution ( P < 0.05). Processed red meat did not exhibit a similar association. CONCLUSION: Higher red meat usual intake was associated with an increased risk of MetS and elevated serum ferritin levels.
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Ingestão de Alimentos , Ferritinas/sangue , Síndrome Metabólica/epidemiologia , Carne Vermelha/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Síndrome Metabólica/etiologia , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Adulto JovemRESUMO
Continuous silicon carbide fiber-reinforced silicon carbide ceramic matrix composites (SiCf/SiC) are promising as thermal structural materials. In this work, the microstructure and static mechanical properties of 3D-SiCf/SiC with PyC, SiC, and PyC/SiC and without an interface prepared via polymer infiltration and pyrolysis (PIP) were investigated systematically in this paper. The results show that the microstructure and static mechanical properties of SiCf/SiC with an interphase layer were superior to the composites without an interlayer, and the interface debondings are existing in the composite without an interphase, resulting in a weak interface bonding. When the interphase is introduced, the interfacial shear strength is improved, the crack can be deflected, and the fracture energy can be absorbed. Meanwhile, the shear strength of the composites with PyC and PyC/SiC interfaces was 118 MPa and 124 MPa, respectively, and showing little difference in bending properties. This indicates that the sublayer SiC of the PyC/SiC multilayer interface limits the binding state and the plastic deformation of PyC interphase, and it is helpful to improve the mechanical properties of SiCf/SiC.
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Fibroblast growth factor-inducible-14 (Fn14), a receptor for tumor necrosis-like weak inducer of apoptosis, is expressed in the neurons of dorsal root ganglion (DRG). Its mRNA is increased in the injured DRG following peripheral nerve injury. Whether this increase contributes to neuropathic pain is unknown. We reported here that peripheral nerve injury caused by spinal nerve ligation (SNL) increased the expression of Fn14 at both protein and mRNA levels in the injured DRG. Blocking this increase attenuated the development of SNL-induced mechanical, thermal, and cold pain hypersensitivities. Conversely, mimicking this increase produced the increases in the levels of phosphorylated extracellular signal-regulated kinase ½ and glial fibrillary acidic protein in ipsilateral dorsal horn and the enhanced responses to mechanical, thermal, and cold stimuli in the absence of SNL. Mechanistically, the increased Fn14 activated the NF-κB pathway through promoting the translocation of p65 into the nucleus of the injured DRG neurons. Our findings suggest that Fn14 may be a potential target for the therapeutic treatment of peripheral neuropathic pain.
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NF-kappa B/metabolismo , Neuralgia/metabolismo , Células Receptoras Sensoriais/metabolismo , Transdução de Sinais , Receptor de TWEAK/metabolismo , Animais , Células Cultivadas , Gânglios Espinais/metabolismo , Gânglios Espinais/patologia , Ligadura , Masculino , Camundongos , Microinjeções , Neuralgia/patologia , Limiar da Dor , Traumatismos dos Nervos Periféricos/metabolismo , Traumatismos dos Nervos Periféricos/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Nervos Espinhais/metabolismo , Nervos Espinhais/patologiaRESUMO
AIM OF STUDY: Several studies have evaluated the correlation between glutathione S-transferase mu-1 (GSTM1), GST theta-1 (GSTT1) polymorphisms and oral cancer in Chinese people. However, the results are inconsistent. To assess the effects of GSTM1, GSTT1 null genotypes on the risk for development of oral cancer in the Chinese population, a meta-analysis was performed. MATERIALS AND METHODS: Studies were identified using PubMed and Chinese databases through February 2016. The associations were assessed with pooled odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: This meta-analysis included six studies with 1306 oral cancer cases and 1484 controls. In the overall analysis, no significant association between GSTM1, GSTT1 polymorphisms and oral cancer was found in the Chinese population. In the subgroup analyses by geographic areas and source of controls, significant risk was found between GSTM1 null genotype and oral cancer in Mainland China (OR = 2.715, 95% CI = 2.17-3.38), but not in Taiwan China. CONCLUSION: Our meta-analysis suggested that GSTM1 null genotype might be associated with an increased risk of developing oral cancer in individuals from Mainland China.
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Povo Asiático/genética , Predisposição Genética para Doença , Glutationa Transferase/genética , Neoplasias Bucais/genética , China , Humanos , Polimorfismo de Nucleotídeo Único , TaiwanRESUMO
Damage to the endothelial glycocalyx is a critical factor in increased pulmonary vascular permeability, which is the basic pathological feature of acute respiratory distress syndrome (ARDS). Neferine (Nef), a bisbenzylisoquinoline alkaloid isolated from green seed embryos of Nelumbo nucifera Gaertn, has extensive pharmacological activity. In this study, we showed that Nef reduced lung-capillary permeability, down-regulated the production of cytokines (IL-1ß, IL-6, TNF-α, and IL-10) and inhibited the activation of the NF-κB signaling pathway in mice with lipopolysaccharide (LPS)-induced ARDS. Further analysis indicated that Nef provided protection against endothelial glycocalyx degradation in LPS-induced ARDS mice (in vivo) and in LPS-stimulated human umbilical vein endothelial cells (in vitro). The glycocalyx-protective effect of Nef may be initiated by suppressing the production of mitochondrial ROS (mtROS) and decreasing oxidative damage. Nef was also found to promote glycocalyx restoration by accelerating the removal of mtROS in endothelial cells in LPS-induced ARDS. These results suggested the potential of Nef as a therapeutic agent for ARDS associated with Gram-negative bacterial infections and elucidated the mechanisms underlying the protection and restoration of the endothelial glycocalyx.
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OBJECTIVE: To study injuries involving brachial plexus and its branches. METHODS: 66 cases collected from 2003 to 2005 in our department were analyzed statistically. RESULTS: 94% of injuries involved young adult males; 94% were blunt force injuries; 34% involved both nerve and bone mainly involving ulnar nerve and ulnar bone (50%); 40% of the injured nerves received electromyogram and 15 nerves were diagnosed with injuries clinically. CONCLUSION: Forensic determination on severity of brachial plexus injuries mainly depends on movement recovery of limb. The best time for forensic appraisal is 20 d post operation+L (length of nerve severed distally)/R (growth rate)+90 d.